Hepatotoxicity of antiviral agents

Because most therapeutic agents used for viral infections are relatively new, experience with their adverse effects is still evolving. Hepatic toxicity has not been among the most important concerns with this class of drugs so far. Liver damage has been increasingly noted with accumulating experience, especially with antiretroviral drugs and those used to treat chronic hepatitis (e.g., fialuridine), but it is often difficult to distinguish between effects of therapy and of the underlying disease. It is important for clinicians to be aware of the possibility of hepatotoxicity in such situations, and further reporting of adverse experiences should contribute to more definitive evaluation of the potential influence of antivirals on liver function.     

'Multifrequency' location and clustering of sequence patterns from proteins

In previous work, we have shown that a set of characteristics, defined as (code frequency) pairs, can be derived from a protein family by the use of a signal-processing method. This method enables the location and extraction of sequence patterns by taking into account each (code frequency) pair individually. In the present paper, we propose to extend this method in order to detect and visualize patterns by taking into account several pairs simultaneously. Two 'multifrequency' methods are described. The first one is based on a rewriting of the sequences with new symbols which summarize the frequency information. The second method is based on a clustering of the patterns associated with each pair. Both methods lead to the definition of significant consensus sequences. Some results obtained with calcium-binding proteins and serine proteases are also discussed.     

The MUC2 gene product: a human intestinal mucin

Sera from 82 cases of leptospirosis (confirmed by micro-agglutination tests or IFAT) and 108 patients with other diseases were investigated using the microcapsule agglutination test (MCAT) for leptospirosis. The overall sensitivity (90.2%), specificity (96.3%), positive predictive value (94.9%), negative predictive value (92.9%), and accuracy of the MCAT (93.7%) were encouraging. MCAT is simple, can be performed by unskilled personnel with minimum laboratory facilities, and produces results in 3 h. MCAT would be a reliable serodiagnostic test for rapidly screening individuals for leptospirosis, in various geographical areas of Thailand.     

Central poststroke pain and Wallenberg''s lateral medullary infarction: frequency, character, and determinants in 63 patients

BACKGROUND: Questionnaire-based surveys from several countries have consistently detected adverse health associated with home dampness and mould growth. METHODS: To test the validity of questions commonly used to indicate the presence of indoor mould, questionnaires were administered in 403 homes where dust samples were taken for viable fungi and air samples for ergosterol. RESULTS: Geometric mean concentrations of the total viable fungi were 255 (SE 116) x 10(3) CFU/g when mouldy odours were reported and 155 (SE 55) when odours were not reported (P = 0.01). Similarly, reported water damage was associated with a 50% increase (P = 0.06). Geometric mean concentrations of the predominantly indoor-source fungi, Aspergillus plus Penicillium, were twice as high when mould or mildew was reported than when not mentioned (P = 0.01). The presence of reported mould or water damage was unrelated to the presence of detectable levels of ergosterol. There was evidence for reporting bias: in the presence of low concentrations of viable fungi in dust, respondents reporting allergies were more likely to report visible mould growth (odds ratio [OR] = 1.8, 95% confidence interval [CI]: 0.9-3.5, P = 0.10. In the presence of elevated concentrations of dust fungi, respondents who smoked were less likely to report visible mould growth, (OR = 0.4, 95% CI: 0.2-0.7, P = 0.005). CONCLUSIONS: Reported mould, water damage, and mouldy odours were associated with elevated levels of indoor fungi. However, inaccuracy was high and there was evidence of a systematic reporting bias. Future research should concentrate on developing accurate objective measures of exposure to fungi, and then use this information to develop valid questionnaires. Currently, objective measures not questionnaires, are recommended to clarify the health effects of indoor fungi.     

Limited expansion of the (CAG)n repeat of the Huntington gene: a premutation (?)

Pantoprazole is a specific inhibitor of the H+/K(+)-ATPase of the gastric parietal cell. The dose-dependency of a range of pantoprazole pharmacokinetic characteristics was studied. Twelve healthy male subjects were given 10, 20, 40 and 80 mg pantoprazole intravenously according to a randomized, single blind, 4-period change-over scheme. The area under the concentration vs time curve (AUC) and the maximum serum concentration (Cmax) showed a linear increase in line with the dose. Apparent volume of distribution (Vd area), clearance (Cl) and terminal half-life (t1/2) were independent of the dose. The dose-independent elimination of pantoprazole was attributed to the lack of interaction of the drug with cytochrome P450. In clinical practice, a good predictable response, as well as a low potential for interaction with other drugs might be expected.     

Prevention of endometrial hyperplasia by progesterone during long-term estradiol replacement: influence of bleeding pattern and secretory changes

OBJECTIVE: To determine the relative influences of induction of withdrawal bleedings secretory transformation, and reduction of mitosis in glands on prevention of endometrial hyperplasia during long-term hormonal replacement therapy. DESIGN: Observational expanded clinical case report. SETTING: Reproductive Endocrine Department of Hospital Necker, Paris, France, and Pathology Department of Women's Hospital, Los Angeles County and University of Southern California Medical Center, Los Angeles, California. PATIENTS: Postmenopausal women seeking treatment for symptomatic menopause. INTERVENTIONS: Endometrial biopsy and/or ambulatory hysteroscopy. MAIN OUTCOME MEASURE: Endometrial histology including progestational maturation patterns and glandular epithelial mitosis rates. Macroscopic endometrial appearance. RESULTS: The use of larger doses of E2 and P induced more marked secretory changes and more frequent withdrawal bleeding than the lower doses. There was no evidence of endometrial hyperplasia after 5 years of E2/P replacement therapy independently of bleeding pattern or progestational maturation. Consistent reduction of mitosis rates in glandular epithelium was found after 9 or more days of P administration in each cycle. CONCLUSIONS: Control of endometrial growth is mainly related to control of mitosis in glands by a relatively low doses of P. Induction of withdrawal bleeding and endometrial secretory transformation, which require larger doses of Progesterone, do not provide additional benefit for prevention of hyperplasia. Induction of amenorrhea with a relatively low dose of P may be offered to women seeking hormone replacement therapy with similar levels of safety.     

A mammalian adaptor protein with conserved Src homology 2 and phosphotyrosine-binding domains is related to Shc and is specifically expressed in the brain

The Shc adaptor protein, hereafter referred to as ShcA, possesses two distinct phosphotyrosine-recognition modules, a C-terminal Src homology 2 (SH2) domain and an N-terminal phosphotyrosine-binding (PTB) domain, and is itself phosphorylated on tyrosine in response to many extracellular signals. Phosphorylation of human ShcA at Tyr-317 within its central (CH1) region induces binding to the Grb2 SH2 domain and is thereby implicated in activation of the Ras pathway. Two shc-related genes (shcB and shcC) have been identified in the mouse. shcB is closely related to human SCK, while shcC has not yet been found in other organisms. The ShcC protein is predicted to have a C-terminal SH2 domain, a CH1 region with a putative Grb2-binding site, and an N-terminal PTB domain. The ShcC and ShcB SH2 domains bind phosphotyrosine-containing peptides and receptors with a specificity related to, but distinct from, that of the ShcA SH2 domain. The ShcC PTB domain specifically associates in vitro with the autophosphorylated receptors for nerve growth factor and epidermal growth factor. These results indicate that ShcC has functional SH2 and PTB; domains. In contrast to shcA, which is widely expressed, shcC RNA and proteins are predominantly expressed in the adult brain. These results suggest that ShcC may mediate signaling from tyrosine kinases in the nervous system, such as receptors for neurotrophins.